Exosomes and Signaling Nanovesicles from the Nanofiltration of Preconditioned Adipose Tissue with Skin-B® in Tissue Regeneration and Antiaging: A Clinical Study and Case Report.

Background and Objectives: This three-year clinical trial aimed to demonstrate that only the signaling vesicles produced by ADSCa, containing mRNA, microRNA, growth factors (GFs), and bioactive peptides, provide an advantage over classical therapy with adipose disaggregate to make the tissue regeneration technique safer due to the absence of interfering materials and cells, while being extremely minimally invasive. The infiltration of disaggregated adipose nanofat, defined by the Tonnard method, for the regeneration of the dermis and epidermis during physiological or pathological aging continues to be successfully used for the presence of numerous adult stem cells in suspension (ADSCa). An improvement in this method is the exclusion of fibrous shots and cellular debris from the nanofat to avoid inflammatory phenomena by microfiltration. Materials and Methods: A small amount of adipose tissue was extracted after surface anesthesia and disaggregated according to the Tonnard method. An initial microfiltration at 20/40 microns was performed to remove fibrous shots and cellular debris. The microfiltration was stabilized with a sterile solution containing hyaluronic acid and immediately ultrafiltered to a final size of 0.20 microns to exclude the cellular component and hyaluronic acid chains of different molecular weights. The suspension was then injected into the dermis using a mesotherapy technique with microinjections. Results: This study found that it is possible to extract signaling microvesicles using a simple ultrafiltration system. The Berardesca Scale, Numeric Rating Scale (NRS), and Modified Vancouver Scale (MVS) showed that it is possible to obtain excellent results with this technique. The ultrafiltrate can validly be used in a therapy involving injection into target tissues affected by chronic and photoaging with excellent results. Conclusions: This retrospective clinical evaluation study allowed us to consider the results obtained with this method for the treatment of dermal wrinkles and facial tissue furrows as excellent. The method is safe and an innovative regenerative therapy as a powerful and viable alternative to skin regeneration therapies, antiaging therapies, and chronic inflammatory diseases because it lacks the inflammatory component produced by cellular debris and fibrous sprouts and because it can exclude the mesenchymal cellular component by reducing multiple inflammatory cytokine levels.

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine.

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy.

A Comprehensive Review on the State of the Art of Breast Cancers in Italy.

Breast cancer (BC) currently represents one of the most prevalent cancers among women worldwide and the leading cause of cancer death among women, also negatively affecting the quality of life (QoL) in patients. Over the past two decades, BC research has led to extraordinary advances in our understanding of the disease, resulting in more effective treatments. However, its occurrence is still increasing. Several new treatments are now under development worldwide, but they are not devoid of well-- known side effects, and a great number of patients develop endocrine resistance. Nevertheless, the design and synthesis of more suitable strategies and new drugs to treat breast cancers, overcome resistance and side effects, and obtain better therapeutic outcomes are needed. In this review, we summarize the therapies and the clinical studies currently ongoing in Italy for the treatment of BCs, mainly HER2+ MBC, HER2-low MBC, and TNBC, focusing on the most recent ones, also in consideration of diverse facets, including some aspects related to QoL. Finally, some studies related to the usefulness of physical activity in BC will be cited.

Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung by inducing an increase in cAMP concentrations. Piclamilast and rolipram are known selective inhibitors of PDE4, which are unfortunately endowed with common side effects, such as nausea and emesis. The selective inhibition of the phosphodiesterase 4B (PDE4B) subtype may represent an intriguing technique for combating this highly contagious disease with fewer side effects. In this article, molecular docking studies for the selective inhibition of the PDE4B enzyme have been carried out on 21 in-house compounds. The compounds were docked into the pocket of the PDE4B catalytic site, and in most cases, they were almost completely superimposed onto piclamilast. Then, in order to enlarge our study, drug-likeness prediction studies were performed on the compounds under study.

Antibiotic-Resistant ESKAPE Pathogens and COVID-19: The Pandemic beyond the Pandemic.

Antibacterial resistance is a renewed public health plague in modern times, and the COVID-19 pandemic has rekindled this problem. Changes in antibiotic prescribing behavior, misinformation, financial hardship, environmental impact, and governance gaps have generally enhanced the misuse and improper access to antibiotics during the COVID-19 pandemic. These determinants, intersected with antibacterial resistance in the current pandemic, may amplify the potential for a future antibacterial resistance pandemic. The occurrence of infections with multidrug-resistant (MDR), extensively drug-resistant (XDR), difficult-to-treat drug-resistant (DTR), carbapenem-resistant (CR), and pan-drug-resistant (PDR) bacteria is still increasing. The aim of this review is to highlight the state of the art of antibacterial resistance worldwide, focusing on the most important pathogens, namely Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae, and their resistance to the most common antibiotics.

Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review.

Soft tissue regeneration holds significant promise for addressing various clinical challenges, ranging from craniofacial and oral tissue defects to blood vessels, muscle, and fibrous tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising tool in regenerative medicine due to their unique characteristics and potential to differentiate into multiple cell lineages. This comprehensive review explores the role of MSCs in different aspects of soft tissue regeneration, including their application in craniofacial and oral soft tissue regeneration, nerve regeneration, blood vessel regeneration, muscle regeneration, and fibrous tissue regeneration. By examining the latest research findings and clinical advancements, this article aims to provide insights into the current state of MSC-based therapies in soft tissue regenerative medicine.

Natural Products for the Prevention, Treatment and Progression of Breast Cancer.

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.

Drugs for COVID-19: An Update.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh known human coronavirus, and it was identified in Wuhan, Hubei province, China, in 2020. It caused the highly contagious disease called coronavirus disease 2019 (COVID-19), declared a global pandemic by the World Health Organization (WHO) on 11 March 2020. A great number of studies in the search of new therapies and vaccines have been carried out in these three long years, producing a series of successes; however, the need for more effective vaccines, therapies and other solutions is still being pursued. This review represents a tracking shot of the current pharmacological therapies used for the treatment of COVID-19.

Adipose Autologous Micrograft and Its Derived Mesenchymal Stem Cells in a Bio Cross-Linked Hyaluronic Acid Scaffold for Correction Deep Wrinkles, Facial Depressions, Scars, Face Dermis and Its Regenerations: A Pilot Study and Cases Report.

The aim of this clinical study was to demonstrate that through a micrograft of viable adipose tissue cells microfiltered at 50 microns to exclude fibrous shoots and cell debris in a suspension of cross-linked hyaluronic acid, we were able to improve visible imperfections of the dermis and to improve clinically observable wrinkles, with a beneficial effect also in the extracellular matrix (ECM). Background and Objectives: With the passage of time, the aging process begins, resulting in a progressive impairment of tissue homeostasis. The main reason for the formation of wrinkles is the involution of the papillary dermis, as well as the loss of stem cell niches with compromise of the extra-cytoplasmic matrix (ECM), and the loss of hyaluronic acid, which helps to maintain the shape and resistance and that is contained in the connective tissue. Materials and Methods: This study involved 14 female patients who underwent dermal wrinkle correction and bio-regeneration over the entire facial area through a suspension containing 1.0 mL of viable micrografts from adipose tissue in a 1.0 mL cross-linked hyaluronic acid. To verify the improvement of the anatomical area concerned over time, the various degrees of correction obtained for wrinkles, and in general for texture, were objectively evaluated by using a Numeric Rating scale (NRS) 10-0, a modified Vancouver scale and a Berardesca scale. Results: The Berardesca, NRS and Modified Vancouver scales showed that with this technique it was possible to obtain excellent results both when the suspension was injected into wrinkles with the linear retrograde technique, and when it was injected with the micropomphs technique to correct furrows, with the intent to revitalize the tissue through progenitors with adult stemness markers. Conclusions: The combination of microfragmented and microfiltered adipose tissue and cross-linked hyaluronic acid at 50 microns is safe new method to treat soft tissue defects such as deep wrinkles.

Surgical treatment of undifferentiated soft tissue sarcoma in a young 17-year-old woman: A case report.

This case report describes the clinical case of a 17-year-old woman with an undifferentiated soft tissue sarcoma in the left supratrocanteric area. The young woman came for observation at our plastic surgery hospital with a large vascular mass visible on her left side which also made walking difficult. Our patient reports the onset of the mass about two months earlier and its growth very quickly. In this case report, we will analyze the demolitive and reconstructive surgical procedures in order to guarantee our patient radical surgery and the possibility of continuing radiotherapy and any specific chemotherapy to avoid the risk of relapse and metastasis over time.

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.

Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies.

Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.